Direct evidence for the activation of phospholipase Cγ1 by in vivo treatment with morphine in the mouse periaqueductal gray matter

The aim of the present study was to investigate whether in vivo morphine treatment could participate in the activation of phospholipase Cγ1 (PLCγ1) isoform in the mouse periaqueductal gray matter (PAG) which can be accompanied by antinociceptive responses induced by morphine. As well as μ-opioid receptor-like immunoreactivity (MOR-IR), moderate PLCγ1-like immunoreactivity (PLCγ1-IR) was noted in the mouse PAG section. After s.c. treatment with morphine, the intensive PLCγ1-IR was detected in the cell surface of the positive cells. Treatment s.c. with morphine produced a robust increase in the number of phosphorylated-PLCγ1 (p-PLCγ1) expressing cells in the PAG. Deletion of PLCγ1 gene by i.c.v. pretreatment with antisense oligodeoxynucleotide against PLCγ1 revealed a significant inhibition of supraspinal antinociception induced by a selective μ-opioid receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO). Furthermore, i.c.v. pretreatment with a specific antibody to PLCγ1 caused a concentration-dependent attenuation of antinociception produced by i.c.v. treatment with either morphine or DAMGO. These findings suggest that in vivo morphine treatment can activate PLCγ1 isoform in the mouse PAG which can be, at least in part, associated with the expression of supraspinal antinociception induced by μ-opioid receptor agonists in the mouse. [Copyright &y& Elsevier]